Carbon tetrabromide → HCID 59231920, compound

HRID 1099259Notes

Reaction equation

HRID 1099259 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([Br:15])[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13]O)[N:6]2[N:5]=[CH:4][N:3]=1.C(Br)(Br)(Br)[Br:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Br:15][C:8]1[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][Br:17])[N:6]2[C:7]=1[C:2]([NH2:1])=[N:3][CH:4]=[N:5]2

Participants

5

Reactant 3

HCID 11205Carbon tetrabromide2×HCID 11776Triphenylphosphine2×HCID 59231966HCID 59231966, compound

Product 1

HCID 59231920HCID 59231920, compoundYield 64.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-Amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-propan-1-ol (1.20 g, 4.43 mmol) in anhydrous THF (22 mL) at 0° C. was added carbon tetrabromide (1.62 g, 4.87 mmol, 1.1 eq) and triphenylphosphine (1.16 g, 4.43 mmol, 1.0 eq). After 5 minutes the ice bath was removed and the reaction mixture was stirred at RT for 1 hour. Then another 0.1 equivalents of both carbon tetrabromide (0.15 g, 0.44 mmol) and triphenylphosphine (0.12 g, 0.44 mmol) were added. The reaction was stirred another hour at ambient temperature before it was filtered to remove some solid which was rinsed with some THF. The combined filtrate and rinse were concentrated at reduced pressure to give a crude product which was purified by MPLC on 120 g of silica gel eluted with a gradient from 0-100% EtOAc in hexane to give 950 mg (64.2%) of desired product as a white solid after evaporation of best fractions which eluted from 55-65% EtOAc. 1H-NMR (DMSO-d6) 7.84 (s, 1H), 6.65 (s, 1H), 3.54 (t, 2H, J=6.4), 2.94 (t, 2H, J=6.4), and 2.16 (q, 2H, J=6.4); MS LC-MS [M+H]+=333.3/335.1/337.1, RT=2.77 min. Evidence showed in the NMR and the LC-MS for about 16% contamination with 5,6-dibromo-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine which came from an analogous contaminant (3-(4-Amino-5,6-dibromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-propan-1-ol) in the starting material. Products that came from this contaminant were removed by chromatography of the product of step 5 below.

Workup

  1. customAfter 5 minutes the ice bath was removed
  2. stirringThe reaction was stirred another hour at ambient temperature before it
  3. filtrationwas filtered
  4. customto remove some solid which
  5. washwas rinsed with some THF
  6. washThe combined filtrate and rinse
  7. concentrationwere concentrated at reduced pressure
  8. customto give a crude product which
  9. customwas purified by MPLC on 120 g of silica gel
  10. washeluted with a gradient from 0-100% EtOAc in hexane

Sources & evidence

ORD record
ord-dba27f8f81494322a5a0fc08f9678669
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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